Scott-Burden T, Resink T J, Hahn A W, Bühler F R
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030.
J Cardiovasc Pharmacol. 1990;16 Suppl 7:S17-20.
Vascular smooth muscle cells (VSMCs), unlike cardiac or skeletal myocytes, are capable of undergoing reversible phenotypic modulation from "contractile" to "proliferative/synthetic" cells in vivo. We have investigated the ability of angiotensin II (Ang II) to influence this process via modulation of extracellular matrix synthesis. Ang II induced a rapid (within 2 h), dose (10(-6)-10(-9) M)-dependent stimulation (14-fold) of thrombospondin (TSP) gene expression in rat VSMCs in the absence of additional factors. This was followed by an enhanced platelet-derived growth factor (PDGF) A chain and transforming growth factor-beta (TGF beta) gene expression. These effects of Ang II could be negated by the simultaneous addition of saralasin (IC50 approximately 10(-9) M for Ang II at 10(-7) M) to cells. Transcription levels for TSP were further enhanced (to 28 X control values) by 6 h, at which time the synthesis of PDGF A chain mRNA was maximal. Although exposure of cells to TSP (5 X 10(-8) M) stimulated signal transduction pathways, it did not enhance levels of either PDGFA or TGF beta transcripts. The glycoconjugate content of extracellular matrices elaborated by cells chronically exposed to Ang II was elevated compared to control cultures and there was a small increase in cell number.
与心肌细胞或骨骼肌细胞不同，血管平滑肌细胞（VSMC）在体内能够经历从“收缩型”到“增殖/合成型”细胞的可逆表型调节。我们研究了血管紧张素II（Ang II）通过调节细胞外基质合成来影响这一过程的能力。在没有其他因素的情况下，Ang II在大鼠VSMC中诱导血小板反应蛋白（TSP）基因表达快速（2小时内）、剂量（10^(-6)-10^(-9) M）依赖性刺激（14倍）。随后血小板衍生生长因子（PDGF）A链和转化生长因子-β（TGFβ）基因表达增强。Ang II的这些作用可通过同时向细胞中添加沙拉新（在10^(-7) M时对Ang II的IC50约为10^(-9) M）而被消除。TSP的转录水平在6小时时进一步增强（达到对照值的28倍），此时PDGF A链mRNA的合成达到最大值。虽然将细胞暴露于TSP（5×10^(-8) M）刺激了信号转导途径，但它并没有提高PDGFA或TGFβ转录本的水平。与对照培养物相比，长期暴露于Ang II的细胞所产生的细胞外基质的糖缀合物含量升高，并且细胞数量略有增加。
